Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects.

Wogonin, a flavone in the roots of Scutellaria baicalensis, reduced etoposide-induced apoptotic cell death in normal cells, such as bone marrow cells and thymocytes. On the other hand, wogonin potentiated the proapoptotic or cytotoxic action of etoposide in tumor cells, such as Jurkat, HL-60, A549, and NCI-H226. These contradictory actions of wogonin on apoptosis are distinguished by normal or cancer cell types.

Inhibition of P-glycoprotein by wogonin is involved with the potentiation of etoposide-induced apoptosis in cancer cells.

Etoposide induces apoptotic cell death in normal and cancer cells. This apoptosis plays a role not only in anticancer effects but also in adverse reactions, such as myelosuppression. Because we had previously found that wogonin, a flavone found in a plant, suppresses thymocyte apoptosis induced by etoposide, we examined the effect of this flavone in cancer cells.

[ARTCEREB irrigation and perfusion solution for cerebrospinal surgery: pharmacological assessment using human astrocytes exposed to test solutions].

ARTCEREB irrigation and perfusion solution (Artcereb) is a preparation intended for the irrigation and perfusion of the cerebral ventricles, and it is therefore important to evaluate the effects of Artcereb on brain cells. In vitro assessment of the effects of Artcereb in cell cultures of human fetal astrocytes was conducted in comparison with normal saline and lactated Ringer's solution. The effects of exposure to Artcereb were evaluated based on microscopic images of the mitochondria stained with rhodamine 123.

Wogonin prevents glucocorticoid-induced thymocyte apoptosis without diminishing its anti-inflammatory action.

The effect of wogonin, a flavone highly purified from the roots of Scutellaria baicalensis, on apoptotic cell death was re-evaluated in rat thymocytes. This flavone inhibited glucocorticoid-induced apoptotic changes such as DNA fragmentation, phosphatidylserine translocation, and nuclear condensation in rat thymocytes. Similar inhibition was also observed in apoptosis induced by other inducers such as etoposide.

Wogonin, a plant flavone, potentiates etoposide-induced apoptosis in cancer cells.

Etoposide, a podophylotoxin anticancer agent, induces apoptotic cell death in normal and cancer cells. Etoposide-induced apoptosis plays a role in not only anticancer effect but also adverse reaction, such as myelosuppression. Since we have found that wogonin, a flavone found in Scutellaria baicalensis Georgi, prevents thymocyte apoptosis induced by various compounds including etoposide, we examined the effect of this flavone on etoposide-induced apoptosis in cancer cells.

Wogonin prevents immunosuppressive action but not anti-inflammatory effect induced by glucocorticoid.

Glucocorticoid, such as dexamethasone, has anti-inflammatory and immunosuppressive action as major pharmacological effects. The latter action caused by lymphocyte apoptosis is not only a therapeutic effect but also an adverse reaction. Wogonin, a plant flavone found in Scutellaria baicalensis Georgi, inhibited dexamethasone-induced apoptotic changes, such as DNA fragmentation, nuclear condensation, phosphatidylserine translocation, and caspase activation in rat thymocytes.

Cationic surfactants induce apoptosis in normal and cancer cells.

Cationic surfactants, such as benzalkonium chloride and benzethonium chloride, possess quaternary ammonium salt. These surfactants have antimicrobial action and are used as a preservative and an antiseptic. The positively charged polar head of cationic surfactants seems to play a role in the antimicrobial action of these compounds.

Effect of selenium-deficient diet on tubular epithelium in normal rats.

Selenium (Se) deficiency reduces glutathione peroxidase (GPx) activity, resulting in increased oxidative stress. We examined how Se deficiency induces renal injury via oxidative stress over time during the Se-deficient period. Seventy-two male Wistar rats were divided into two groups and fed either a control or Se-deficient diet.

Effect of selenium on Cisplatin-induced nephrotoxicity in rats.

Cisplatin (CP), a commonly used antineoplastic drug, is nephrotoxic. CP-induced nephrotoxicity involves oxidative pathways. A deficiency of selenium (Se) reduces glutathione peroxidase (GPx) activity resulting in oxidative stress.

Expression of multidrug resistance proteins and accumulation of cisplatin in human non-small cell lung cancer cells.

In order to understand and overcome multidrug resistance (MDR) of human non-small cell lung cancer (NSCLC), mRNA and protein expression levels of P-glycoprotein (MDR1), multidrug resistance-associated protein 1 (MRP1), and lung resistance-related protein (LRP) were investigated and compared with the chemosensitivity and the intracellular/intranuclear cisplatin accumulation of three NSCLC cell lines (Ma-10, Ma-31, and Ma-46). Ma-31 was more resistant than Ma-10 and Ma-46 to cisplatin, carboplatin, etoposide, and paclitaxel. The mRNA level of MDR1 was extremely low, and MDR1 protein was not detected in all cell lines.

Thymocyte apoptosis induced by various compounds including YO-2 is accompanied by a change in chromatin structure.

To elucidate the role of chromatin structure in DNA fragmentation during apoptosis, we have examined whether chromatin structural change is observed after treatment with proapoptotic compounds. Analysis of the circular dichroism (CD) spectrum of the soluble chromatin from dexamethasone-treated thymocytes revealed a decrease in alpha-helical content. Mifepristone, an antagonist of glucocorticoid receptor, prevented both the change in chromatin structure and DNA fragmentation induced by dexamethasone.

Overexpression of constitutive signal transducer and activator of transcription 3 mRNA in cisplatin-resistant human non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) often shows intrinsic multidrug resistance, which is one of the most serious problems in cisplatin-based adjuvant chemotherapy. Recently, the constitutive activation of signal transducer and activator of transcription (STAT) factors has been found in a variety of human cancers. In the present study, the mRNA expression of STATs in various human NSCLC cell lines was investigated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) to determine whether STATs can be implicated in cisplatin resistance and apoptosis inducibility.

The structure-activity relationship of various YO compounds, novel plasmin inhibitors, in the apoptosis induction.

We have previously reported that YO-2, a selective plasmin inhibitor, induces thymocyte apoptosis. To elucidate the mechanism of YO-2-induced apoptosis, other YO compounds with different plasmin inhibitory action were tested for the pro-apoptotic activity in this study. The treatment of rat thymocytes with the YO compounds which had the hydrophobic but not the hydrophilic moiety at the C-terminal increased DNA fragmentation, the number of condensed nuclei and caspase-3-like activity.

Terfenadine induces thymocyte apoptosis via mitochondrial pathway.

The treatment of rat thymocytes with 10 microM terfenadine resulted in a significant increase in DNA fragmentation. The DNA fragmentation induced by terfenadine was dependent on its concentration and incubation time. In terfenadine-treated cells, the translocation of phosphatidylserine from the inside of plasma membrane to the outside, an early event of the apoptotic process, and chromatin condensation, the morphological characterization of apoptotic cell death, were observed.

Involvement of the change in chromatin structure in thymocyte apoptosis induced by phosphorylation of histones.

The inhibitors of protein phosphatase such as calyculin A and okadaic acid induced thymocyte apoptosis. DNA fragmentation was increased in the nuclei from thymocytes treated with calyculin A, which accelerated phosphorylation of histones. Judging from the circular dichroism analysis, the structure of soluble chromatin was changed by the treatment with calyculin A.

Involvement of histone phosphorylation in apoptosis of human astrocytes after exposure to saline solution.

We have previously found using inhibitors of protein phosphatase that phosphorylation of histones may be involved in thymocyte apoptosis. In this study, we examined whether histone modification occurs in astrocyte apoptosis induced by a pathological condition in the absence of drug. Incubation of cultured human astrocytes with growth medium for 24 h after exposure to saline solution for 30 min induced an increase in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and nuclear condensation, biochemical and morphological hallmarks of apoptotic cell death.

Thymocyte apoptosis induced by phosphorylation of histones is associated with the change in chromatin structure to allow easy accessibility of DNase.

The inhibitors of protein phosphatase such as calyculin A and okadaic acid induce the apoptotic cell death in rat thymocytes. To clarify the molecular mechanism of these inhibitor-induced apoptosis, the effect of calyculin A on DNA fragmentation in the isolated nuclei were studied. A significant increase in DNA fragmentation was observed in the nuclei prepared from the cells treated with calyculin A that caused histone hyperphosphorylation.

Roles of cathepsins in reperfusion-induced apoptosis in cultured astrocytes.

Astrocytic apoptosis may play a role in the central nervous system injury. We previously showed that reperfusion of cultured astrocytes with normal medium after exposure to hydrogen peroxide (H(2)O(2))-containing medium causes apoptosis. This study examines the involvement of the lysosomal enzymes cathepsins B and D in the astrocytic apoptosis.

Heat shock inhibits hydrogen peroxide-induced apoptosis in cultured astrocytes.

Heat shock proteins (HSPs) have been shown to act as inhibitors of apoptosis, but this anti-apoptotic effect is not known in the central nervous system. Prior heat shock has been demonstrated to protect astrocytes from cell death in a model of reperfusion injury (Brain Res. 735 (1996) 265).

The nitric oxide donor NOC12 protects cultured astrocytes against apoptosis via a cGMP-dependent mechanism.

We examined the effect of 3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC12), a nitric oxide (NO) donor, on apoptosis in cultured astrocytes. Reperfusion after hydrogen peroxide (H2O2) exposure caused a decrease in cell viability, loss of mitochondrial membrane potential, caspase-3 activation, DNA ladder formation, and nuclear condensation. NOC12 at 10-100 microM significantly attenuated these apoptotic changes, while the NO donor at 1 mM caused cell injury and exacerbated the H202-induced cell injury.

A selective plasmin inhibitor, trans-aminomethylcyclohexanecarbonyl-L-(O-picolyl)tyrosine-octylamide (YO-2), induces thymocyte apoptosis.

The treatment of rat thymocytes with YO-2, a novel inhibitor of plasmin, resulted in an increase in DNA fragmentation. DNA fragmentation was also induced by another YO compounds such as YO-0, -3, -4 and -5. These YO compounds are the inhibitor of plasmin activity.